Studies designed to uncover molecular aspects of cytotoxicity for several new agents are in progress. The interaction of an acridine derivative (NSC-141549) with nucleic acids was investigated and was found to be selective for A:T base pairs as determined by inhibition of various nucleic acid polymerases using synthetic templates of known composition. This was confirmed by thermal stability studies utilizing these same templates. An analog of uridine, 3-deazauridine (NSC-126849) was found to be phosphorylated in vivo to the corresponding nucleotides by mouse tissues and i.p. implanted L1210 cells. The in vivo phosphorylation rates were greater in L1210 cells than in normal cells and there was an accumulation of 3-deazauridine triphosphate in the L1210 cells. An extension of the pharmacologic disposition studies of inosine dialdehyde (NSC-118994) demonstrated this agent to cross-link plasma proteins and to bind to RBC membranes. These reactions would explain the increased thrombin time and the positive Coomb's reaction exhibited by patients receiving this agent. Cytosine arabinoside 5'-methylphosphonate was synthesized as an analog of araCMP to circumvent resistance to araC. This compound is a competitive inhibitor of dCMP kinase but is not phosphorylated by this enzyme.